Early versus delayed enteral nutrition in mechanically ventilated patients with circulatory shock: a nested cohort analysis of an international multicenter, pragmatic clinical trial.

INTRODUCTION: Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. METHODS: We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating < 48 h from ICU admission and DEN > 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site. RESULTS: We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18-93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups. CONCLUSION: In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.

Procalcitonin: A promising tool or just another overhyped test?

Sepsis is the leading cause of death worldwide. Timely administration of antibiotics is recognized as the cornerstone in the management of sepsis. However, inappropriate use of antibiotics may lead to adverse effects and the selection of drug-resistant pathogens. Microbiological cultures remain the gold standard to diagnose infection despite their low sensitivity and the intrinsic delay to obtain the results. Certain biomarkers have the benefit of rapid turnover, potentially providing an advantage in timely diagnosis leading to accurate treatment. Over the last few decades, there is an ongoing quest for the ideal biomarker in sepsis. Procalcitonin (PCT), when used alone or alongside additional clinical information, has shown to be a promising tool to aid in the diagnosis and management of patients with sepsis. In February 2017, the Food and Drug Administration (FDA) approved the use of PCT to guide antibiotic treatment in lower respiratory tract infections and sepsis. Despite a good negative predictive value for bacterial infection, the utility of PCT-guided antibiotic initiation is conflicting at best. On the other hand, the use of PCT-guided antibiotic discontinuation has shown to reduce the duration of antibiotic use, the associated adverse effects, and to decrease the overall mortality. The current review discusses the history and pathophysiology of procalcitonin, synthesizes its utility in the diagnosis and management of sepsis, highlights its limitations and compares it with other biomarkers in sepsis.

Hospital and intensive care unit management of decompensated pulmonary hypertension and right ventricular failure.

Pulmonary hypertension and concomitant right ventricular failure present a diagnostic and therapeutic challenge in the intensive care unit and have been associated with a high mortality. Significant co-morbidities and hemodynamic instability are often present, and routine critical care unit resuscitation may worsen hemodynamics and limit the chances of survival in patients with an already underlying poor prognosis. Right ventricular failure results from structural or functional processes that limit the right ventricle's ability to maintain adequate cardiac output. It is commonly seen as the result of left heart failure, acute pulmonary embolism, progression or decompensation of pulmonary hypertension, sepsis, acute lung injury, or in the perioperative setting. Prompt recognition of the underlying cause and institution of treatment with a thorough understanding of the elements necessary to optimize preload, cardiac contractility, enhance systemic arterial perfusion, and reduce right ventricular afterload are of paramount importance. Moreover, the emergence of previously uncommon entities in patients with pulmonary hypertension (pregnancy, sepsis, liver disease, etc.) and the availability of modern devices to provide support pose additional challenges that must be addressed with an in-depth knowledge of this disease.

Hospital-Onset Sepsis Warrants Expanded Investigation and Consideration as a Unique Clinical Entity.

Sepsis causes more than a quarter million deaths among hospitalized adults in the United States each year. Although most cases of sepsis are present on admission, up to one-quarter of patients with sepsis develop this highly morbid and mortal condition while hospitalized. Compared with patients with community-onset sepsis (COS), patients with hospital-onset sepsis (HOS) are twice as likely to require mechanical ventilation and ICU admission, have more than two times longer ICU and hospital length of stay, accrue five times higher hospital costs, and are twice as likely to die. Patients with HOS differ from those with COS with respect to underlying comorbidities, admitting diagnosis, clinical manifestations of infection, and severity of illness. Despite the differences between these patient populations, patients with HOS sepsis are understudied and warrant expanded investigation. Here, we outline important knowledge gaps in the recognition and management of HOS in adults and propose associated research priorities for investigators. Of particular importance are questions regarding standardization of research and clinical case identification, understanding of clinical heterogeneity among patients with HOS, development of tailored management recommendations, identification of impactful prevention strategies, optimization of care delivery and quality metrics, identification and correction of disparities in care and outcomes, and how to ensure goal-concordant care for patients with HOS.

Pulmonary arterial hypertension trials put to the test: Using the fragility index to assess trials robustness.

BACKGROUND: Randomized clinical trials (RCTs) are considered the gold standard for evidence-based medicine. The Fragility Index (FI) is a tool to assess the robustness of RCT results. FI was validated for dichotomous outcomes and recent work expanded its use to continuous outcomes. Studying the robustness of RCTs in Pulmonary Arterial Hypertension (PAH) treatments is crucial due to the severity and mortality risks associated with this rare condition. OBJECTIVES: Analyze FI and Fragility quotient (FQ) of significant primary outcomes in PAH RCTs and study FI correlation with sample size and journal impact factor. METHODS: FI and FQ calculation followed by Spearman correlation to assess the correlation between FI and sample size, and FI and impact factor. RESULTS: The median sample size of the 21 trials was 202 patients (IQR 106-267), with 6 trials reporting primary outcomes as dichotomous and 15 reporting continuous primary outcomes. The median FI was 10 (IQR 3-20), and the median FQ was 0.044 (0.026-0.097). A moderate correlation was found between FI and sample size, with r = 0.56; P = 0.008 and FI and journal impact factor (r=0.50; P=0.019). The FI for continuous outcomes was similar to that for dichotomous outcomes. CONCLUSIONS: This study represents the first analysis of the FI and FQ of PAH treatment RCTs, and expands the use of FI to continuous outcomes in this context. The moderate correlation between FI and sample size suggests that increasing sample size alone is partially correlated to a higher FI. The similarity between FI for continuous and dichotomous outcomes supports the broader use of FI in PAH RCTs.

Clinical Implications of Bronchodilator Testing: Diagnosing and Differentiating COPD and Asthma-COPD Overlap.

BACKGROUND: Bronchodilation testing is an important component of spirometry testing, and omitting this procedure has potential clinical implications toward diagnosing respiratory diseases. We aimed to estimate the impact of bronchodilator testing in accurately diagnosing COPD and differentiating COPD from asthma-COPD overlap (ACO). METHODS: The National Health and Nutrition Examination Survey data were analyzed from 2007-2012. Airflow limitation was defined by FEV1/FVC < 0.7. Subjects with pre-bronchodilator airflow limitation were classified into pre-but-not-post-bronchodilator airflow limitation and post-bronchodilator airflow limitation groups. Spirometry-confirmed COPD was defined by persistent airflow limitation on post-bronchodilator spirometry. The American Thoracic Society (ATS) and the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) definitions were used to identify possible ACO subjects. RESULTS: We identified 11,763 subjects ≥ 40 y of age eligible for spirometry; 625 of them had a pre-bronchodilator FEV1/FVC < 0.7 and completed post-bronchodilator spirometry that met ATS spirometry quality standards. A total of 244 (39%) of these subjects had only pre-not-post-bronchodilator airflow limitation, thereby not meeting the definition of spirometrically confirmed COPD. The prevalence of ACO was 7.6% using the modified ATS definition and 19.8% using the modified SEPAR criteria. When bronchodilator testing-based criteria were excluded from ATS and SEPAR definitions, the number of ACO subjects decreased by 39.3% and 12.3%, respectively. CONCLUSIONS: Spirometry with bronchodilation is an important element in the accurate diagnosis of ACO and COPD. Spirometry performed without bronchodilator testing may lead to an estimated misclassification of ACO by 7.6% to 19.8% and overdiagnosis of COPD by 39%.

[Significance of the "isolated anti-HBc" serological pattern determinated by the serological response to the vaccination against Hepatitis B]. / Significado del patrón serológico "anti-HBc aislado" determinado por la respuesta serológica a la vacunación contra Hepatitis B.

Frequently Blood Bank donors are found to have a presence of Total Anti-Bc in the serum in the absence of the Hepatitis B surface antigen (HBsAg) and the Hepatitis B Surface Antigen (Anti-Bs) antibody. This study was designed to determine the serological response to the vaccination against the Hepatitis B virus, and evaluate the effectiveness of the vaccine in such cases, taking into consideration that the protective antibody titers for Hepatitis B are measured in levels above 10 mUl/ml.Thirty-one patients with the HBsAg negative/Anti-Bs negative/Antil-Bc positive serological patterns received three doses of the recombinant DNA vaccine (Hepavax Gene 20 microg), in a 0, 1, 2 months vaccination schedule. Anti-HBs levels were taken 30 days after the application of the last dose. After the 3 doses of the vaccine, the Anti-HBs levels were > 100 mUl/ml in 89% of the cases, > 500 in 50% and > 1000 in 14.3% of the vaccinated patients. Only 3 patients (9.7%) did not show serological response 30 days after the application of the last dose of the vaccine. In conclusion, 90% of the patients administered the HBsAg negative/Anti-HBs negative/Anti-HBc positive serological patterns, obtained Anti-HBs levels considered protectors ( > 10 mUl/m).

Significado del patrón serológico Anti-HBc Aislado determinado por la respuesta serológica a la vacunación contra Hepatitis B / Significance of the Isolated Anti-HBc serological pattern determined by the serological response to the vaccination against Hepatitis B

Con frecuencia se encuentran donantes de Banco de sangre con presencia en suero del anti-HBc total, en ausencia del Antígeno de superficie (HBsAg) y el anticuerpo contra el antígeno de superficie (Anti-HBs). Se diseñó el presente estudio para determinar la respuesta serológica a la vacunación contra el virus de la hepatitis B y evaluar la efectividad de la vacuna en dichos casos, considerando que los títulos protectores en Hepatitis B se miden en niveles superiores a 10 mUl/ml. Se incluyeron 31 pacientes con el patrón serológico HBsAg(-)/Anti-HBs(-)Anti-HBc(+). Se les administró 3 dosis de la vacuna ADN recombinante (Hepavax Gene 20 ug), siguiendo el esquema 0,1,2 meses. Se midieron los niveles de Anti-HBs 30 días después de la aplicación de la última dosis. Luego de las 3 dosis de vacuna los niveles de Anti-HBs fueron > 100 mUl/ml en el 89 por ciento, >500 en el 50 por ciento y >1000 en el 14,3 por ciento de los pacientes vacunados. Sólo 3 pacientes (9.7 por ciento) no presentaron respuesta serológica 30 días después de la aplicación de la última dosis de vacuna. En conclusión, se obtuvieron niveles de Anti-HBs, considerados protectores (>10 mUl/ml), en el 90 por ciento de pacientes con el patrón serológico HBsAg (-) Anti-HBs (-) Anti-HBc (+).